Subclinical Reactivation of Cytomegalovirus Drives CD4+CD28null T-Cell Expansion and Impaired Immune Response to Pneumococcal Vaccination in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.
Dimitrios Chanouzas,Dimitrios Chanouzas,Michael Sagmeister,Michael Sagmeister,Sian E Faustini,Peter Nightingale,Alex G. Richter,Charles J. Ferro,M D L Morgan,M D L Morgan,Paul Moss,Lorraine Harper,Lorraine Harper +12 more
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TLDR
In this article, a proof-of-concept open-label clinical trial, 38 CMV-seropositive AAV patients were randomized to receive valacyclovir for 6 months or no intervention.Abstract:
Background Infection is the leading cause of death in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Expansion of CD4+CD28null T cells is associated with increased risk of infection and mortality, but is only present in cytomegalovirus (CMV)-seropositive individuals. We hypothesized that subclinical CMV reactivation drives CD4+CD28null T-cell expansion, that this is associated with impaired immune response to heterologous antigens, and that antiviral therapy may ameliorate this. Methods In a proof-of-concept open-label clinical trial, 38 CMV-seropositive AAV patients were randomized to receive valacyclovir for 6 months or no intervention. CMV reactivation was measured monthly in plasma and urine. CD4+CD28null T cells were enumerated at baseline and at 6 months. At 6 months, 36 patients were vaccinated with a 13-valent pneumococcal vaccine. Serotype-specific immunoglobulin G was assayed before and 4 weeks postvaccination to calculate the antibody response ratio. Results Valacyclovir treatment suppressed subclinical CMV reactivation and reduced CD4+CD28null T-cell proportion. CD4+CD28null T-cell reduction correlated with improved vaccine response, whereas CMV reactivation associated with reduced response to vaccination. Furthermore, expansion of CD4+CD28null T cells was associated with a reduction in the functional capacity of the CD4 compartment. Conclusions Suppression of CMV may improve the immune response to a T-cell-dependent pneumococcal vaccination in patients with AAV, thus offering potential clinical benefit. Clinical trials registration NCT01633476.read more
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ANCA-associated vasculitis.
A. Richard Kitching,Hans-Joachim Anders,Neil Basu,Elisabeth Brouwer,Jennifer Gordon,David Jayne,Joyce Kullman,Paul A. Lyons,Peter A. Merkel,Caroline O. S. Savage,Ulrich Specks,Renate Kain +11 more
TL;DR: The classification of AAVs and the pathogenetic mechanisms, diagnosis and treatment of these debilitating conditions are discussed and a need for targeted therapies with fewer adverse effects is needed.
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CD28 null CD4 T-cell expansions in autoimmune disease suggest a link with cytomegalovirus infection.
Aalia S. Bano,Alejandra Pera,Ahmad Almoukayed,Thomas H.S. Clarke,Sukaina Kirmani,Kevin A. Davies,Florian Kern +6 more
TL;DR: It is demonstrated that the common herpes virus, cytomegalovirus (CMV), not ageing, is the major driver of this subset of cytotoxic T cells.
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Accelerated immunosenescence in rheumatoid arthritis: impact on clinical progression
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Viral Infections and Systemic Lupus Erythematosus: New Players in an Old Story.
TL;DR: A causal link between viral infections and autoimmunity has been studied for a long time and the role of some viruses in the induction or exacerbation of systemic lupus erythematosus (SLE) in genetically predisposed patients has been proved as discussed by the authors.
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Human Cytomegalovirus and Autoimmune Diseases: Where Are We?
Francesca Gugliesi,Selina Pasquero,Gloria Griffante,Sara Scutera,Camilla Albano,Sergio Fernando Castillo Pacheco,Giuseppe Riva,Valentina Dell'Oste,Matteo Biolatti +8 more
TL;DR: In this article, the authors summarize the available literature on the various ADs arising from or exacerbating upon HCMV infection, focusing on the potential role of immune activation at disease onset.
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TL;DR: The 2009 European League Against Rheumatism recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) have been updated and 15 recommendations were developed, covering general aspects, such as attaining remission.
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Long-term patient survival in ANCA-associated vasculitis
Oliver Flossmann,Annelies E. Berden,Kirsten de Groot,Chris Hagen,Lorraine Harper,Caroline Heijl,Peter Höglund,David Jayne,Raashid Luqmani,Alfred Mahr,Chetan Mukhtyar,Charles D. Pusey,Niels Rasmussen,Coen A. Stegeman,Michael Walsh,Kerstin Westman +15 more
TL;DR: Patients with ANCA-associated vasculitis treated with conventional regimens are at increased risk of death compared with an age- and sex-matched population.
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CD4+ CD7- CD28- T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity.
TL;DR: In vivo expanded CD4+ T cells were autoreactive to ubiquitously distributed autoantigens and responded in an autologous mixed lymphocyte reaction, and T cell clones isolated from selected patients proliferated to Autologous peripheral blood adherent cells.